Background Melanoma is the most aggressive skin malignancy with high morbidity. Anti-programmed cell death protein 1 (PD-1) monotherapy has been applied in metastatic melanoma, however, most patients do not respond to anti-PD-1 and the availability of the present approved biomarkers is limited.

Methods Here we combined the transcriptomic and clinical data in 163 advanced melanoma patients receiving anti-PD-1 from phs000452 (122 patients) as the training and internal validation cohort, and PRJEB23709 (41 patients) as the external validation cohort, respectively.

Results 74,243circular RNAs (circRNA) were identified with NCLscan and CIRCexplorer2, 70 circRNAs significantly associated with progression-free survival and overall survival as novel putative candidates to predict the survival benefit of immunotherapy. The prognostic circRNAs signature (HSA_CIRCpedia_1497, HSA_CIRCpedia_12559, HSA_CIRCpedia_43640, HSA_CIRCpedia_43070, and HSA_CIRCpedia_21660) was determined with LASSO regression. This signature was a prognostic factor of overall survival and progression-free survival among advanced melanoma patients, and the concordance indexes also confirms its credibility and accuracy. Enrichment analysis showed that immune response and currently known pathways were enriched.

Conclusions We constructed and validated a novel prognostic circRNAs signature to serve as a predictor for advanced melanoma patients treated with anti-PD-1 immunotherapy.